Its northern terminus is at a T-intersection with U.S. Route 50 (US 50) nearly 2.75 miles (4.43 km) southwest of Albany.

Originally, this highway started in downtown Middleport at the intersection of 2nd Avenue, the former routing of SR 7, and Mill Street.

It followed Mill Street to the northwest, which becomes known as Bradbury Road once it leaves the village.

It then followed the entirety of its current alignment, coming to an end at the predecessor to US 50, SR 26.

[2][3] By 1969, in conjunction with the completion of a new SR 7 bypass of Middleport and Pomeroy, the SR 143 designation was removed from the portions located to the south of its current southern terminus, thus resulting in the highway taking on the shape it has today.